Clinical interventions based on positive psychology are increasingly the subject of scientific literature. In this review we argue that, both for theoretical and practical reasons, it is necessary to take into account negative and positive aspects of human functioning for a better understanding of clinical issues. Three relevant and complementary models of psychological well-being are discussed in regard to their direct implications for psychotherapy interventions: Seligman's model of the three ways to happiness (Seligman, 2002), Ryff's multidimensional model of psychological well-being (Ryff, 1995) and Deci and Ryan's motivational model of well-being (Deci and Ryan, 2000). Positive interventions in the clinical arena should be strongly guided by empirical data derived from the existing abundant research on happiness and psychological well-being. Furthermore, promising new interventions and programs to enhance people's well-being, some of which are described in this review, should be tested with the most stringent designs (namely, randomized clinical trials) in order to prove their efficacy. Finally, we discuss the implications of positive interventions to tackle important clinical problems (e.g., relapses and recurrences) and present some challenges that future research in this emerging field needs to address.