This historical minireview traces the development and application of methods for gene-targeted and site-directed mutagenesis of photosynthesis genes in cyanobacteria (mainly Synechocystis sp. PCC 6803). This approach allowed important data to be obtained on the structure and function of Photosystem I and Photosystem II complexes. I describe some of the major contributions of molecular genetics and subsequent mutant analysis in the 1980s and early 1990s that led to substantial advances in our knowledge of basic principles regarding the organization of the photosynthetic apparatus. This molecular-genetic research on cyanobacteria has initiated a fresh wave of photosynthesis research and created a solid foundation for rapid progress at the threshold of the twenty-first century.