Recently, the high analytical power provided by the new HRMS instruments (working in the MS or MS/MS mode, stand alone or hyphenated with separation techniques) is making more feasible the characterization of plant secondary metabolites. In this regard, HRMS-based techniques are becoming the technique of choice, since they are capable of answering many questions regarding the analytical characterization of secondary metabolites, usually found in very complex matrices, including their structural elucidation and quantification in a very fast and sensitive way. In this manuscript we will provide a critical and updated revision of this topic covering the works published in the last 4 years (2015–2018), including the different configurations in which HRMS may be used (stand alone or hyphenated), the data treatment, the strategies for the identification of unknown metabolites, the current software for structure elucidation, as well as the last trends and future outlooks in this hot area of research. •Recent HRMS-based applications for plant secondary metabolites are reviewed.•Stand alone or hyphenated HRMS configurations are discussed and compared.•A broad variety of databases and HRMS-data mining strategies are presented.•Future challenges in dereplication and metabolite profiling are emphasized.