The disease burden from Legionella spp. infections has been increasing in many industrialized countries and, despite decades of scientific advances, ranks amongst the highest for waterborne diseases. We review here several key research areas from a multidisciplinary perspective and list critical research needs to address some of the challenges of Legionella spp. management in engineered environments. These include: (i) a consideration of Legionella species diversity and cooccurrence, beyond Legionella pneumophila only; (ii) an assessment of their environmental prevalence and clinical relevance, and how that may affect legislation, management, and intervention prioritization; (iii) a consideration of Legionella spp. sources, their definition and prioritization; (iv) the factors affecting Legionnaires' disease seasonality, how they link to sources, Legionella spp. proliferation and ecology, and how these may be affected by climate change; (v) the challenge of saving energy in buildings while controlling Legionella spp. with high water temperatures and chemical disinfection; and (vi) the ecological interactions of Legionella spp. with other microbes, and their potential as a biological control strategy. Ultimately, we call for increased interdisciplinary collaboration between multiple research domains, as well as transdisciplinary engagement and collaboration across government, industry, and science as the way toward controlling and reducing Legionella-derived infections.