Regulation of gene transcription and cell differentiation often induces drastic phenotypes in living organisms. External, precise control over these processes through small organic molecules represents a challenge in chemistry and biology. Our laboratory has been discovering small organic molecules that modulate transcription or differentiation and using them as a tool to understand biological phenomena. This personal perspective summarizes our contributions to chemical biology and chemical genetics in the fields of gene transcription and cell differentiation. Our case studies may foreshadow the promise and the challenge of future drug discovery.