In the last few decades, access to high-resolution mass spectrometry (HRMS) technology has expanded, especially in analytical toxicology where tandem mass spectrometry was considered the “Gold Standard”. Given its selectivity, sensitivity and versatility, HRMS represents a technique of choice for pharmaceuticals analysis. Indeed, specific applications, such as pharmacokinetic and toxicokinetic studies or metabolomics studies (in vitro and in vivo drug metabolism studies), have expanded with the development of the technology. HRMS may also be suited for screening and quantification of pharmaceuticals and in development drugs. The aim of this work was to obtain a clear overview about the interests of HRMS technology applied to the field of analytical toxicology, in particular to the analysis of medicinal drugs. Throughout this review, we explored the potential of HRMS on specific applications such as pharmacokinetic and toxicokinetic studies, metabolomics studies (in vitro and in vivo drug metabolism studies), screening, quantification of medicinal and in the development of drugs. Multiple studies supported the suitability of HRMS for the mentioned applications bringing forward the selectivity, sensitivity and versatility of this technology. On the other side, we stressed the need for the development of new analysis tools allowing for a better processing of the large amount of data generated through HRMS analysis.