OBJECTIVES: Comorbidities are conditions or diseases besides the one of primary interest. A comorbidity index condenses all the coexistent conditions to a single score and comorbidity indexes have been extensively used to adjust analyses for the impact of comorbidities. De Groot and colleagues published a literature review in 2003 listing available indexes and reporting their validity.The objective of this study was to review published methods to measure comorbidity and thereby provide an update of the publication by de Groot and colleagues.  METHODS: A structured search, using as primary search terms comorbidity, multimorbidity, and coexisting disease, was undertaken in Embase.com to identify studies published since 2000 in which an index to measure comorbidity is described. For validity, correlation coefficients, ratios, explained variance, and the area under the receiver operating characteristic curve were used. Regression models predicting future events that were significant or significantly improved after adding comorbidity as a covariate was considered to support validity. Parameters used to assess reliability were among others correlation coefficients. RESULTS: Sixtyfour publications were studied resulting in twentyfive different indexes, to measure comorbidity were identified, compared to the thirteen identified by de Groot and colleagues (2003). In line with previous findings, the Charlson Comorbidity Index (CCI) generated the greatest number of studies and the most consistent results regarding validity and reliability. CCI compiles the weighted mortality association of nineteen different diseases with a number of adaptations for specific circumstances. CONCLUSIONS: The main finding is that the CCI remains the most used and validated index, and also a number of new comorbidity indexes have been identified in this study. Assessment of comorbidity is an area of interest for both health economists and epidemiologists and it seems to be receiving increased attention.