Aim To present the activities of the Agency for Medicinal Products and Medical Devices in the first 5 years of its existence and to define its future challenges. Methods Main activities within the scope of the Agency as a regulatory authority were retrospectively analyzed for the period from 2004-2008. Data were collected from the Agency’s database and analyzed by descriptive statistics. Results The number of issued medicine authorizations rose from 240 in 2004 to 580 in 2008. The greatest number of new chemical and biological entities was approved in 2005. The greatest number of regular quality controls (n = 5833) and special quality controls was performed in 2008 (n = 589), while the greatest number of off-shelf quality controls (n = 132) was performed in 2007. The greatest number of medicine labeling irregularities was found in 2007 (n = 19) and of quality irregularities in 2004 (n = 9). The greatest number of adverse reactions was reported in 2008 (n = 1393). The number of registered medical devices rose from 213 in 2004 to 565 in 2008. Conclusion Over its 5 years of existence, the Agency has successfully coped with the constant increase in workload. In the future, as Croatia enters the European Union, the Agency will have to face the challenge of joining the integrated European regulatory framework.