Lifestyle and social assessment and interventions represent a paradigm shift in clinical and academic healthcare, more deeply addressing comprehensive biopsychosocial–cultural determinants. This chapter explores the fundamental principles of ‘Lifestyle Medicine’ as an evidence-based clinical discipline focused on addressing modifiable lifestyle factors to prevent, treat and in some cases reverse chronic diseases. The text examines the key pillars of lifestyle approaches including nutrition, physical activity, sleep, social connection, substance reduction, mind–body approaches and engagement with the natural world, which are translated into clinical practice and research via behavioural and implementation science. Contemporary trends in chronic disease are discussed alongside behavioural change techniques and principles for implementing lifestyle interventions in clinical practice that support sustainable healthy lifestyles. This chapter also highlights the reciprocal benefits of lifestyle medicine for healthcare practitioners and concludes with an exploration of future directions and research opportunities in this rapidly evolving field. Understanding Lifestyle Medicine provides healthcare professionals with essential tools to address the root causes of today’s most prevalent health challenges.