Introduction: For 30 years, 5-aminosalicylic acid (5-ASA) has been the backbone of therapeutic management in patients with ulcerative colitis (UC). In the biologic era, it still remains the treatment of choice in mild-to-moderate UC. Positioning of this therapeutic class in moderate-to-severe UC is less clear. Areas covered: Several studies demonstrated the ability of 5-ASA to induce endoscopic remission to a similar extent as anti-TNF therapy on the moderate segment of UC. Histologic remission is achieved after induction in up to 45% of patients treated with topical 5-ASA and 30% with oral formulations. Aminosalicylates offer a favorable safety profile compared to that of immunomodulators and biologics. High-dose 5-ASA therapy may be a valuable option for patients with moderately active disease, and physicians should weigh the pros and cons of this strategy in selected patients. Whether aminosalicylates should be continued in combination with thiopurines or biologic therapy remains under debate. Expert opinion: In the era of biologics, aminosalicylates remain the first-line therapy in patients with mild UC, and have to be considered in case of moderate UC, given their favorable risk-benefit profile. We suggest that 5-ASA should be used in moderate patients without poor prognostic factors, while biologics should be preferred otherwise.