Mitochondria, colloquially known as "the powerhouse of the cell", play important roles in production, but also in processes critical for cellular fate such as cell death, differentiation, signaling, metabolic homeostasis, and innate immunity. Due to its many functions in the cell, the mitochondria have been linked to a variety of human illnesses such as diabetes, cancer, and neurodegenerative diseases. In order to further our understanding and pharmaceutical targeting of this critical organelle, effective strategies must be employed to breach the complex barriers and microenvironment of mitochondria. Here, we summarize advancements in mitochondria-targeted probes and therapeutics.