This review focuses on the application of computational fluid dynamics (CFD) in pulmonary drug delivery, particularly for treating asthma and COPD with pharmaceutical aerosols via dry powder inhalers (DPIs). Aerosol drug delivery effectiveness relies on accurate assessment and prediction of particle deposition in the respiratory system. This method is crucial due to the high number of pulmonary disease cases, efficient lung absorption capabilities, lower dosage required, and reduced systemic side effects compared to oral medications. Given the limits of in vivo and in vitro methods, CFD modeling has advanced rapidly over 20 years, especially when combined with discrete phase model (DPM) and discrete element method (DEM) approaches. CFD simulations can correctly account for a wide range of realistic or idealized parameters using numerical solutions of particle and airflow transport equations. Achieving accurate simulations requires avoiding simplifications and approximating real-world conditions, which will soon be more possible with advancing computing tools. The research aims to review numerical modeling of pulmonary drug delivery along the mouth-to-lung pathway, encompassing governing equations, forces, boundary conditions, the influence of lung geometry on CFD modeling, the effects of powder characteristics on aerosolization and pulmonary deposition, validation of computational results with in vitro/in vivo data, and a discussion of current challenges and future prospects.