The format of the original Hamilton Rating Scale for Depression (HAM-D) was unstructured: only general instructions were provided for rating individual items. Over the years, a number of modified versions of the HAM-D have been proposed. They differ not only in the number of items, but also in modalities of administration. Structured versions, including item definitions, anchor points and semi-structured or structured interview questions, were developed. This comprehensive review was conducted to examine the clinimetric properties of the different versions of the HAM-D. The aim was to identify the HAM-D versions that best display the clinimetric properties of reliability, validity, and sensitivity to change. The search was conducted on MEDLINE, Scopus, Web of Science, and PubMed, and yielded a total of 35,473 citations, but only the most representative studies were included. The structured versions of the HAM-D were found to display the highest inter-rater and test-retest reliability. The Clinical Interview for Depression and the 6-item HAM-D showed the highest sensitivity in differentiating active treatment from placebo. The findings indicate that the HAM-D is a valid and sensitive clinimetric index, which should not be discarded in view of obsolete and not clinically relevant psychometric criteria. The HAM-D, however, requires an informed use: unstructured forms should be avoided and the type of HAM-D version that is selected should be specified in the registration of the study protocol and in the methods of the trial.