Several barriers occur among flowering plants to prevent self-fertilization by increasing and maintaining the species genetic variability. From all these barriers, self-incompatibility (SI) is one of the most effective avoiding endogamy. Genetic control in SI relies on the polymorphic S locus, where both pollen and pistil S determinants are encoded. Based on the pollen S phenotype, diploid or haploid, there are two kinds of genetic control in the SI systems: the sporophytic and the gametophytic. In the gametophytic SI systems, two mechanisms are currently unraveled. One exclusive to Papaveraceae and the other one, known as the S-RNase-based SI, which is present in more divergent taxa: Plantaginaceae, Rosaceae, Rubiaceae, Rutaceae, and Solanaceae. The more in-depth studies on the molecular mechanism have been mainly done in Solanaceae, particularly in Petunia and Nicotiana, achieving significant advances by different genetic, molecular, biochemical, and cellular approaches, resulting in two models to encompass further evidence to explain it: the collaborative and the compartmentalization model. Both models, however, seem to be excluding each other. Here we will discuss the evidence and the information around these explanations and will discuss the possibility of why it has been so challenging to find an integrative hypothesis to understand this critical evolutionary process within angiosperms.