Newly synthesized polypeptides contain signals that direct them to the appropriate intracellular organelles and the organelles contain receptors that recognize the signals. Protein synthesis occurs either on free ribosomes or on ribosomes bound to the endoplasmic reticulum. The proteins synthesized on bound ribosomes are co-translationally translocated into the lumen of the endoplasmic reticulum and contain or acquire targeting information for retention in the endoplasmic reticulum or for sorting to lysosomes and other compartments of the secretory and endocytic pathways. Proteins synthesized on free ribosomes remain in the cytosol or contain signals for import into the nucleus, mitochondria or peroxisomes. The nature of the targeting signals and the mechanisms of import are discussed briefly. Examples are given of inborn errors of metabolism caused by incorrect or impaired incorporation of proteins into mitochondria, lysosomes or peroxisomes.