Positive psychological well-being is prospectively associated with superior health outcomes. Positive psychology interventions have promise as a potentially feasible and effective means of increasing well-being and health in those with medical illness, and several initial studies have shown the potential of such programs in medical populations. At the same time, numerous key issues in the existing positive psychology literature must be addressed to ensure that these interventions are optimally effective. These include (1) assessing the nature and scope of PPWB as part of intervention development and application; (2) identifying and utilizing theoretical models that can clearly outline potential mechanisms by which positive psychology interventions may affect health outcomes; (3) determining consistent, realistic targets for positive psychology interventions; (4) developing consistent approaches to the promotion of positive psychological well-being; (5) emphasizing the inclusion of diverse samples in treatment development and testing; and (6) considering implementation and scalability from the start of intervention development to ensure effective real-world application. Attention to these six domains could greatly facilitate the generation of effective, replicable, and easily adopted positive psychology programs for medical populations with the potential to have an important impact on public health.