Diarylethenes (DAEs) represent an important class of photochromes with notable characteristics, like thermally irreversible photoisomerization and high fatigue resistance. Structural diversification of the DAE scaffold has enabled further refinement of photochromic properties and realization of new applications, ranging from advanced materials to tools for studying biological systems. In particular, methods for synthesizing non-symmetric DAE scaffolds, which are typically more challenging to synthesize than their symmetric counterparts, have grown over the past 20 years. These developments are surveyed in this review, with discussion of how access to these compounds has contributed to the improvement of photochromic properties and paved the way for exploring new applications of DAEs. First, non-symmetric DAE structures are classified and their uses and applications are overviewed. Subsequent sections discuss the main strategies that have been used to access non-symmetric DAEs with examples illustrating the impact of non-symmetric DAEs in the growing field of light-controlled molecular systems.