The anti-inflammatory 5-aminosalicylic acid (5-ASA) is the main therapeutic option used in the prevention and treatment of inflammatory bowel diseases. The upper intestinal tract performs rapid and almost complete absorption of this drug when administered orally., making local therapeutic levels of the molecule in the inflamed colonic mucosa difficult to achieve. Micro and nanoparticle systems are promising for 5-ASA incorporation because the reduced dimensions of these structures can improve the drug's pharmacodynamics and contribute to more efficient and localized therapy. Together, the association of these systems with polymers will allow the release of 5-ASA through specific targeting mechanisms to the colon, as demonstrated in mesalazine modified-release dosage form. In this review, the challenges for the oral administration of 5-ASA and the different colon-specific delivery strategies using polymers will be summarized and discussed.