In 2014, with new drugs and regimens becoming available for the treatment of multidrug-resistant (MDR) tuberculosis (TB), the World Health Organization (WHO) recommended that countries should conduct active pharmacovigilance (PV) for these new drugs and regimens. Because of the complexity of MDR-TB treatment, which requires a regimen with multiple TB medicines and a minimum treatment duration of 6 months, the best described and most comprehensive active PV method, cohort event monitoring (CEM), was regarded as too demanding for the countries with the highest burden of MDR-TB. This is because at the time, adverse events (AEs) were known to occur very frequently: 70–90% of patients treated for MDR-TB experienced AEs, and many of them had multiple AEs. Therefore, active drug safety monitoring and management (aDSM), a tiered PV approach, was introduced. The core aDSM package only collects data on serious adverse events (SAEs), while the intermediate package additionally includes the collection of AEs of special interest (AEs that occur frequently among patients treated for MDR-TB or have been associated with the new drugs in clinical studies), and the advanced package collects all AEs of clinical interest. Data from countries that implemented CEM have confirmed that CEM of MDR-TB patients is extremely challenging and that other forms of active PV, like the aDSM core or intermediate package, are better suited. However, health care providers should be encouraged to also report unexpected and previously unknown AEs not included in these packages.