Measurement of drug concentrations and performing therapeutic drug monitoring (TDM) are widely used to optimize efficacy and safety of many commonly used drugs today. Although TDM of first-line antitubercular drugs is used during the treatment of tuberculosis, the extent of any benefit achieved is currently unknown. This review summarizes the available literature describing TDM of first-line treatment agents in patients with tuberculosis and describes clinical associations with achievement of target drug concentrations, including data from special populations. A literature review was conducted for articles describing drug concentration and TDM outcomes for first-line tuberculosis agents in adults. A total of 40 studies were included in the review. Studies were a mixture of controlled trials, observational studies, cross-sectional studies, and case reports. The majority of the studies showed standard dosing does not consistently achieve target concentrations for the first-line antitubercular drugs; however, the clinical implications of this finding are still unclear. Presence of HIV and diabetes mellitus appeared to indicate achievement of lower than target concentrations and this warrants further study in prospective studies. Current published data neither prove nor disprove the utility of TDM for general tuberculosis populations but evidence does not currently support routine measurement of drug concentrations.