Alkaloids are a diverse class of nitrogen-containing metabolites involved in key biotic interactions, such as defense against herbivores and pathogens and the recruitment of pollinators. The Solanaceae family has served as a model for studying alkaloid evolution, due to the varied types of alkaloids it produces, such as nicotinoids, tropane alkaloids (TAs), steroidal glycoalkaloids (SGAs), and capsaicinoids. Recent multi-omics and comparative genomics studies have expanded our understanding of the genetic and evolutionary mechanisms driving alkaloid diversification. These metabolites are produced by specific clades within the family, often in response to selective pressures such as herbivore and pathogen coevolution, which shape alkaloid profiles through both diversification and reduction. Evolutionary processes like genome duplications, rearrangements, and introgressions have also played a significant role in the emergence of new alkaloid pathways, promoting metabolic adaptations. The Solanaceae family exhibits both convergence and divergence in alkaloid production, with certain alkaloids arising independently in different lineages. Notably, biosynthetic gene clusters (BGCs) and gene duplication have been linked to alkaloid diversification, with the structure and function of these regions driving metabolic variability. Furthermore, human domestication of plants such as tobacco and chili peppers has influenced the alkaloid profiles of crop species, particularly in terms of pest resistance and flavor. The evolution of alkaloids in this family has not only shaped plant defense mechanisms but also has important implications for human health and agriculture. This review highlights the dynamic interplay between genetics, ecology, and human influence in the evolution of alkaloids within the Solanaceae family.