This chapter focuses on describing the current converging evidence-base on what is a debilitating, common and costly condition worldwide. Historically, the prevailing understanding of chronic pain was based on a purely biomedical model; however, a plethora of research has now disconfirmed the tenets of this reductionistic model, and pain is now widely understood from a biopsychosocial perspective. Within this framework, a number of biological, psychological, and social risk and protective factors have been found to be of importance. This chapter describes these risks and protective factors, and provides an overview of the empirical findings pertaining to the links between these factors and short- and long-term pain-related outcomes. An approach based on the biopsychosocial model that targets pain from a multidimensional perspective is Cognitive Behavioral Therapy (CBT); the efficacy and cost-effectiveness of this approach across a range of pain types is described, along with needed future directions. More research is needed to advance scientific understanding of the processes underlying the transition from acute to chronic pain, as well as those factors that mediate as well as moderate CBT and other treatment outcomes in order to enhance preventative as well as management interventions.