Mental health professionals have significantly underestimated the importance of lifestyle factors (a) as contributors to and treatments for multiple psychopathologies, (b) for fostering individual and social well-being, and (c) for preserving and optimizing cognitive function. Consequently, therapeutic lifestyle changes (TLCs) are underutilized despite considerable evidence of their effectiveness in both clinical and normal populations. TLCs are sometimes as effective as either psychotherapy or pharmacotherapy and can offer significant therapeutic advantages. Important TLCs include exercise, nutrition and diet, time in nature, relationships, recreation, relaxation and stress management, religious or spiritual involvement, and service to others. This article reviews research on their effects and effectiveness; the principles, advantages, and challenges involved in implementing them; and the forces (economic, institutional, and professional) hindering their use. Where possible, therapeutic recommendations are distilled into easily communicable principles, because such ease of communication strongly influences whether therapists recommend and patients adopt interventions. Finally, the article explores the many implications of contemporary lifestyles and TLCs for individuals, society, and health professionals. In the 21st century, therapeutic lifestyles may need to be a central focus of mental, medical, and public health.