Collaborative practice among health professionals is slowly coming of age, given the global focus on efficiency and effectiveness of care to achieve positive patient outcomes and to reduce the economic burden of fragmented care. Collaborative pharmacy practice (CPP) is accordingly evolving within different models including: disease management, medication therapy management, patient centered medical home, and accountable care organizations. Pharmacist roles in these models relate to drug therapy management and include therapy introduction, adjustment, or discontinuation, patient counseling and education, and identification, resolution, and prevention of problems leading to drug interactions and adverse reactions. Most forms of CPP occur with physicians in various settings. Collaborative practice agreements exist in many states in the US and are mentioned in the International Pharmaceutical Federation policy statement. Impetus for CPP comes from health system and economic concerns, as well as from a regulatory push. There are positive examples in community, ambulatory care, and inpatient settings that have well documented protocols, indicators of care, and measurement and reporting of clinical, economic, and patient reported outcomes; however, implementation of the practice is still not widespread. Conceptual and implementation challenges include health professional training, attitudes, confidence and comfort levels, power and communication issues, logistic barriers of time, workload, proximity, resistance to establish and adopt regulations, and importantly, payment models. Some of the attitudinal and perceptual challenges can be mitigated by incorporation of interprofessional concepts and practice in health profession education. Other challenges need to be addressed across health systems, given the inefficiencies and problems that arise from lack of communication and coordination of patient care including medication nonadherence, errors and patient safety, complexity of compounded health problems, and potential liability. The existing evidence needs to be examined to address some challenges and improve infrastructure for CPP.