During the past decade, patient safety issues during care transitions have gained greater attention at both the local and national level. Readmission rates to U.S. hospitals are high, often because of poor care transitions. Serious adverse drug events (ADEs) caused by an incomplete understanding of changes in complex drug regimens can be an important factor contributing to readmission rates. This paper describes the roles and responsibilities of pharmacists in ensuring optimal outcomes from drug therapy during care transitions. Barriers to effective care transitions, including inadequate communication, poor care coordination, and the lack of one clinician ultimately responsible for these transitions, are discussed. This paper also identifies specific patient populations at high risk of ADEs during care transitions. Several national initiatives and newer care transition models are discussed, including multi- and interdisciplinary programs with pharmacists as key members. Among their potential roles, pharmacists should participate on medical rounds where available, perform medication reconciliation and admission drug histories, apply their knowledge of drug therapy to anticipate and resolve problems during transitions, communicate changes in drug regimens between providers and care settings, assess the appropriateness and patient understanding of drug regimens, promote adherence, and assess health literacy. In addition, this paper identifies barriers and ongoing challenges limiting greater involvement of pharmacists from different practice settings during care transitions. Professional degree programs and residency training programs should increase their emphasis on pharmacists' roles, especially as part of interdisciplinary teams, in improving patient safety during care transitions in diverse practice settings. This paper also recommends that Accreditation Council for Pharmacy Education (ACPE) standards include specific language regarding the exposure of students to issues regarding care transitions and that students have several opportunities to practice the skills needed for effective care transitions. Moreover, reimbursement mechanisms that permit greater pharmacist involvement in providing medication assistance to patients going through care transitions should be explored. Although health information technology offers the potential for safer care transitions, pharmacists' use of information technology must be integrated into the national initiatives for pharmacists to be effectively involved in care transitions. This paper concludes with a discussion about the importance of recognizing and addressing health literacy issues to promote patient empowerment during and after care transitions.