Randomized clinical trials evaluate the efficacy of treatments in selected groups of patients defined by strict inclusion criteria. The value of these trials in predicting therapeutic effectiveness in the natural population of rheumatoid arthritis (RA) patients is limited. The long-term observational studies are designed to complete the knowledge obtained in randomized clinical trials and to assess the effectiveness and tolerability of the treatment in patients who would never have been included in the clinical trial, because of their current disease state, high number of previous DMARD failures, or their comorbidity. The long-term observational studies evaluate the continuation rates of TNF inhibitors in a defined period, intensification of traditional DMARD co-therapy, increase of the anti-TNF dose, change in disease activity over time and long-term safety of the treatment. In recent years, the results of several long-term observational studies, based on national biological agents registries, have been published. The results of these studies are discussed.