The success of anaerobic digestion relies on the presence of highly active methanogenic biomass, requiring effective retention of slow growing anaerobic microorganisms inside bioreactor by decoupling the hydraulic retention time (HRT) from solids residence time (SRT) or the employment of long SRTs in fully mixed systems. So far, flow through systems, i.e. completely stirred tank reactor (CSTR) digesters, and granular sludge bed reactors have been commonly applied for anaerobic treatment of slurries and low particulate matter containing streams, respectively. Physical separation of particulates by membranes is an efficient tool to uncouple SRT from HRT. Anaerobic membrane bioreactor (AnMBR) is a combination of an anaerobic process with membrane units located either inside or outside the reactor. These systems are expected to fill the gap between low loaded slurry digesters and high rate granular sludge bed reactors. AnMBRs are especially suitable when efficient biomass retention cannot be achieved due to wastewater characteristics, inappropriate reactor operation and/or design. AnMBRs provide an excellent treatment efficiency, thanks to the membrane filtration which ensures particulate free effluent. On the other hand, membrane fluxes in AnMBRs are naturally limited by the effectiveness of the filtration process which is impacted by the build-up of a fouling layer in and on the membrane surface. The degree of fouling can be described by the increase in transmembrane pressure (TMP) or by the reduction of filtrate flux due to clogging of membrane pores or dense cake-layer later build-up. The reasons and mitigation possibilities of membrane fouling have received a significant scientific interest for decades. However, thus far, membrane fouling remains the focal point of membrane bioreactor (MBR) studies due to the complexity of phenomenon. The purpose of this thesis is to further increase the understanding of fouling phenomena in AnMBR systems by evaluating the impact of substrate composition and the effect of factors such as SRT on biological performance and sludge filterability. In order to mitigate fouling in AnMBRs, it is of crucial importance to understand the impact of operational conditions on sludge characteristics and filterability. Standard parameters such as capillary suction time (CST), specific resistance to filtration (SRF), and critical flux (CF) was used to evaluate the effect of different operation conditions. Moreover, the influence of high lipid content, acidified and non-acidified wastewaters and nitrogen deficiency on sludge characteristics and filterability was investigated. The SRT had an effect on both biodegradation efficiency and filterability. A higher degree of substrate bioconversion to methane was observed at increased SRT. Controversially, the increase in SRT led to poor filterability due to accumulation of colloids and soluble microbial products (SMP) in the bulk sludge. The filterability parameters such as CST and SRF were found as valuable tools for subjective comparison of operational changes. However, it was difficult to evaluate the relationships between filterability parameters and membrane fouling due to the complexity of fouling and non-linearity of correlations. Thus, it was suggested to evaluate a set of parameters about sludge characteristics and filterability in order to establish a link with membrane fouling. For corn thin stillage and cheese whey permeate as the substrates we observed high COD removal efficiencies, exceeding 95%, which confirms the excellent performance of AnMBRs. However, the hydrolysis products of lipids, i.e. long chain fatty acids (LCFAs), caused reversible inhibition by forming a layer on the bioflocs that retards the transfer of substrate and nutrients. The biomass activity decrease due to LCFA adsorption was almost completely recoverable when the feed was stopped. However, the LCFA adsorption had other consequences on sludge surface characteristics. The results of this thesis showed that LCFA adsorption on biomass increased its hydrophobicity which in turn decreased its fouling propensity. Very likely, owing to the increased hydrophobicity of the flocs there is less interaction with the hydrophilic membrane. Feeding non-acidified substrate to the AnMBR led to a rapid deterioration of the sludge filterability, which was attributed to the proliferation of acidogenic microorganisms on the rapidly fermentable carbohydrates. The abundant presence of single cell acidogens decreased the median particle size of the sludge. Additionally, the food to microorganism ratio (F:M) was found an important parameter impacting sludge filterability. An increase in this parameter resulted in accumulation of soluble microbial products (SMP) which led to deterioration of the supernatant filterability. The experiments carried out with cheese whey revealed that nitrogen content effected both reactor stability and bulk liquid filterability. Nitrogen deficiency limited biomass growth and caused volatile fatty acids (VFA) accumulation, especially propionic acid, even at low organic loads. This was ascribed to metabolic changes which likely caused an adverse effect on syntrophic propionate oxidation. On the other hand sludge filterability rapidly deteriorated when AnMBR was fed with nitrogen supplied whey at a COD:TKN ratio of 50. We observed two distinct fractions of biomass with different particle size distribution, SRF and extracellular polymeric substances (EPS) content. The reduction of sludge filterability was attributed to induced growth of acidogenic biomass on lactose with surplus of nitrogen.