The highly attenuated poxvirus strain modified vaccinia virus Ankara (MVA) has reached maturity as a vector delivery system and as a vaccine candidate against a broad spectrum of diseases. This has been largely recognized from research on virus-host cell interactions and immunological studies in pre-clinical and clinical trials. This review addresses the studies of MVA vectors used in phase I/II clinical trials, with the aim to provide the main findings obtained on their behavior when tested against relevant human diseases and cancer and also highlights the strategies currently implemented to improve the MVA immunogenicity. The authors assess that MVA vectors are progressing as strong vaccine candidates either alone or when administered in combination with other vectors.