Since the beginning of the third millennium the incidence of Sexually Transmitted Infections (STIs) is rising in Europe and in Belgium, and this after a steady decline in the second half of last century. It concerns new or lesser known diseases such as Hepatitis C and Lymphogranuloma venereum (LGV) and 'old' diseases such as gonorrhoea and syphilis, occurring in specific risk groups. In this article we give an update of the diagnostic means and therapeutic challenges that are of interest for the clinician. Besides these (re)-emerging diseases we touch on Human Papillomavirus (HPV) and Herpes Simplex (HSV). This selection of diseases is based on the daily experience of the clinicians working in the STI clinic of the Institute of Tropical Medicine in Antwerp. Data and clinical guidelines are derived from the Scientific Institute of Public Health in Brussels, the European and American Centers for Disease Control and Prevention, and the Guidelines of the Flemish Agency for Care and Health. New evolutions in diagnostics, prevention and treatment options make it necessary to regularly update the knowledge of this group of diseases, especially when they are complicated by HIV co-infection. As the incidence of neither HIV nor STIs seem to decrease in Belgium and Europe, it remains necessary to stay aware of the state-of-the-art management.