Plant metabolites are compounds that have been traditionally classified as hormones or as either primary or specialized (secondary) metabolites based on their chemical and structural properties as well as on their whole-plant effects. Accordingly, they are generally regarded as being required for plant growth and development and environmental responses and/or acting as mere by-products of metabolic pathways with no significant role. However, emerging evidence based mostly on recent physiological, biochemical and evolutionary studies sheds new light on the widespread and diverse or overlapping functions of many of these metabolites, leading to a re-evaluation of their classifications and roles in plants. This special issue explores this theme in more detail and contains three reviews and seven research articles that provide a glimpse into the evolution of metabolic enzymes resulting in the structural diversity of metabolites evident in nature (for more details, see editorial by Hirai et al.).