Ulcerative colitis is a chronic inflammatory and debilitating disease requiring lifelong treatment. First-line therapy for ulcerative colitis is 5-aminosalicylic acid, which suffers from poor patient adherence outside the clinical trial setting. Formulations to deliver 5-aminosalicylic acid to the disease activity site, both orally and topically, are often inconvenient and require multiple daily dosing. Such regimens can interfere with normal life and reduce the overall quality of life, negatively impacting on treatment adherence and leading to poorer long-term outcomes. These include increased morbidity with an elevated risk of symptomatic relapse, possible greater risk of colorectal cancer and higher overall costs of care. Ulcerative colitis patients cite treatment regimen complexity, tablet quantity and dose frequency as key negative influencers of adherence. Solutions to these issues include addressing patient concerns, simplifying daily regimens and utilizing new formulations such as micropellet and multimatrix oral formulations, rectal gel and once-daily suppository formulations. This review examines the prevalence and impact of non-adherence to 5-aminosalicylic acid therapy among patients with ulcerative colitis, as well as drug delivery strategies that may enhance dosing regimens to improve patient acceptability, adherence and long-term clinical outcomes. It is a combination of understanding patient behaviour, recognizing signs of non-adherent behaviour and utilizing management strategies to change behaviour that will improve patient outcomes.