Therapy with biologicals for the management of rheumatic diseases has improved treatment options and dramatically increased expectations of patients and doctors. Remission is a reasonable therapeutic aim, as well as inhibition of progression of structural damage. In 2012, five TNF-α inhibitors and four other biologicals targeted against Il-1, IL-6, B-lymphocytes and cell-cell interaction, have become available. Safety data for biological therapy are reassuring, based on a large amount of study data and data collected from national registries. The most important side-effect is a slightly increased tendency to infections (up to doubled in the first treatment year, depending on other factors such as previous infections and comorbidities). An increased risk for cancer (with the exception of preliminary data supporting a possible increase of skin cancer) has not been observed for patients treated with anti-TNF-α. Screening for tuberculosis as well as completing of vaccinations is necessary before starting treatment.