The anticancer agents fluorouracil, raltitrexed, irinotecan and oxaliplatin show limited efficacy in the treatment of colorectal cancer and may be associated with substantial toxicity. Therefore, the prevention and reduction of chemotherapy-induced adverse effects is of major significance, in accordance with the increasing concern for the quality of life of patients with cancer. Therapeutic drug monitoring of fluorouracil and chronomodulation of fluorouracil and oxaliplatin, have been effective in reducing the incidence and gravity of adverse effects in several clinical trials. However, these concepts have not been implemented in clinical practice yet. At the present time, dose adaptation and supportive measures are the main tools for toxicity control in the treatment of colorectal cancer. In this review, supportive measures for alleviation of the adverse effects of fluorouracil, raltitrexed, irinotecan and oxaliplatin, respectively, are described, based on study results. The main adverse effects of these agents are myelosuppression, oral mucositis, diarrhoea, acute cholinergic syndrome, nausea and emesis, neurotoxicity, hand-foot syndrome and other cutaneous adverse effects, ocular toxicity, cardiotoxicity, small bowel toxicity, asthenia, elevated liver transaminase levels and alopecia. The incidence and gravity of these adverse effects are more or less related to the agent and administration schedule involved. The supportive measures and recommendations include the use of specific drugs, alterations of administration schedule and several nonpharmacological methods. In addition, guidelines for dosage adjustments when toxicity occurs are presented. For optimal management of adverse effects, patients should be considered individually, while patients, nurses and physicians should cooperate to identify and treat adverse effects in an early stage of their development.