The majority of colorectal cancer patients receive chemotherapy either to palliate advanced unresectable disease or to reduce the risk of recurrence after radical surgery. Thanks to the improvements in systemic chemotherapy, in the last 20 years the median survival time for patients with unresectable metastatic disease has indeed progressively increased from less than 6 to almost 24 months and recurrences after radical surgery in patients with early-stage tumors have been halved. Although colorectal cancer incidence increase with aging, there is limited scientific evidence based on prospective clinical trials to guide the management of elderly colorectal cancer patients. In addition, aging is a continuum process making strict cut-off difficult to define and homogeneous subgroups hard to identify. There is significant heterogeneity also as regards comorbidities, overall physical ability, mental health and functional status. Specific guidelines for the medical treatment of elderly colorectal cancer patients are therefore difficult to draw. While fit patients are generally treated with adult protocols and frail individuals rarely receive chemotherapy, managing the intermediate vulnerable patients requires a careful balance between the biological and psycho-social costs of treatment, the aggressiveness of the tumor and its perception by the patient. In this review, the major achievements of chemotherapy in the treatment of colorectal cancer will be described and the available data addressing the extension of these chemotherapy programs to elderly patients will be discussed. Special emphasis will be given to the development of specific treatment strategies depending on the degree of disease aggressiveness. Empirical suggestions to adapt the chemotherapy programs developed for adult fit patients to subjects with various degrees of vulnerability and frailty will also be given along with practical indications for the use of specific chemotherapeutic agents in the presence of some common elderly-related comorbidities.