The occurrence of several geriatric conditions may influence the efficacy and limit the use of drugs prescribed to treat chronic conditions. Functional and cognitive impairment, geriatric syndromes (i.e. falls or malnutrition) and limited life expectancy are common features of old age, which may limit the efficacy of pharmacological treatments and question the appropriateness of treatment. However, the assessment of these geriatric conditions is rarely incorporated into clinical trials and treatment guidelines. The CRIME (CRIteria to assess appropriate Medication use among Elderly complex patients) project is aimed at producing recommendations to guide pharmacologic prescription in older complex patients with a limited life expectancy, functional and cognitive impairment, and geriatric syndromes, and providing physicians with a tool to improve the quality of prescribing, independent of setting and nationality. To achieve these aims, we performed the following: (i) Existing disease-specific guidelines on pharmacological prescription for the treatment of diabetes, hypertension, congestive heart failure, atrial fibrillation and coronary heart disease were reviewed to assess whether they include specific indications for complex patients; (ii) a literature search was performed to identify relevant articles assessing the pharmacological treatment of complex patients; (iii) A total of 19 new recommendations were developed based on the results of the literature search and expert consensus. In conclusion, the new recommendations evaluate the appropriateness of pharmacological prescription in older complex patients, translating the recommendations of clinical guidelines to patients with a limited life expectancy, functional and cognitive impairment, and geriatric syndromes. These recommendations cannot represent substitutes for careful clinical consideration and deliberation by physicians; the recommendations are not meant to replace existing clinical guidelines, but they may be used to help physicians in the prescribing process.