The mitochondrial inner membrane of most organisms studied so far contains about a dozen proteins made by the mitochondrial genetic system and on the order of 10 proteins imported from the cytoplasm. This review briefly describes the two major pathways by which proteins made inside or outside the mitochondria are inserted into the inner membrane. These pathways were discovered only during the past few years; one of them involves a novel family of chaperone-like proteins in the mitochondrial intermembrane space. Import of proteins from the cytoplasm into mitochondria occurs by distinct routes that are dictated by the properties and final destination of each protein within the mitochondria (1–3). However, most of the different routes described until recently have been variants of the general “matrix pathway.” In this pathway, a protein carrying a positively charged amphiphilic helix at its N terminus is bound by cytosolic chaperones, delivered to an array of import receptors on the mitochondrial surface, and then transported across two distinct, hetero-oligomeric protein translocation channels, the TOM complex in the outer membrane and the TIM23 complex in the inner membrane. During transport, the two complexes are transiently linked by the translocating precursor chain (4, 5). Transport across the TOM complex appears to be driven by binding of the basic N-terminal “presequence” to a series of acidic receptor domains of increasing avidity (“acid chain hypothesis”) (6, 7); insertion of the presequence into the TIM23 complex is driven electrophoretically by the potential across the inner membrane; and complete transport of the precursor into the matrix is driven by an ATP-powered import motor attached to the inner mouth of the TIM23 complex. Proteins destined for compartments other than the matrix can diverge from the general matrix pathway at different points (8–10). Some proteins destined for the outer membrane can arrest in the TOM complex and then escape into the outer membrane (11); and some intermembrane space proteins can arrest in the TIM23 complex and then be proteolytically released into the intermembrane space (8). A few years ago it seemed likely that a variation of this general matrix pathway would also sort proteins to the inner membrane. According to this view, a protein destined for the inner membrane would arrest in the TIM23 complex and escape “sidewise” into the phospholipid bilayer of the inner membrane. So far, however, no inner membrane protein has been shown to follow such a pathway. Arrest in the TIM23 complex has only been found for some proteins destined for the intermembrane space.