Inflammatory bowel diseases (IBD) have developed to become a major global health problem. Ulcerative colitis (UC) is one of two main types of IBD, and >90% of patients suffering from mild or moderate forms of UC are treated with mesalazine, a well-tolerated and cost-effective drug. To allow oral administration, the drug has to be protected from resorption before it can reach the affected sites in the colon. The drug is therefore released from most currently used medications either constantly slow (time-dependent) or triggered by an increased pH during gastrointestinal transition. Both variants are widely used in clinical practice and it is surprising that they have not yet been compared directly in a large clinical study. In this overview, the evidence that may suggest preferential use of one type of mesalazine formulation over the other in general or for defined subgroups of patients is summarized and evaluated. Data from in vitro modelling of drug release and measurements of drug concentrations in colonic mucosa suggest that in many cases, constant release and pH-dependent formulations are of similar therapeutic efficiency; however, pH-triggered release may be superior in patients with proctitis-type UC or sites of inflammation in the proximal colon. Additionally, patients with a long gastric residence time, slow small intestinal transition, disease-related diarrhea or sensitivity to systemic adverse effects may benefit more from pH-dependent release formulations. In general, medications based on both concepts show similar efficacies, but the pH-dependent release formulations seem to be more robust in the treatment of a not further classified group of patients with UC. Future comparative clinical studies are required to clearly define the subgroups of patients that should be treated preferably with constant or pH-dependent release formulations of mesalazine.