This article presents overviews of adherence or compliance in clinical care and research, focusing on the need to enhance research adherence. The scope of the clinical research enterprise and costs of conducting clinical research are summarized. Costs associated with suboptimal adherence in clinical care and research also are addressed, along with their implications for enhancing adherence. Methodological problems and statistical challenges (including intent-to-treat) associated with poor adherence are reviewed. Addressing social factors, regimen characteristics, behavioral patterns, and systems issues can affect adherence. Strategies for enhancing adherence in clinical research subjects, including pre-randomization screening, behavioral and educational interventions, monitoring, and enhancing subjects' status and contingencies for adhering are discussed. Integrating adherence-enhancing strategies throughout research phases, from pre-randomization screening during recruitment to endpoint, has the potential to improve the quality and outcome of research while limiting costs.