Plant metabolism is strongly determined by plastids. Besides hosting the photosynthetic machinery, these endosymbiotic organelles synthesize starch, fatty acids, amino acids, nucleotides, tetrapyrroles, and isoprenoids. Enzymes involved in plastid-localized metabolic pathways are encoded by the nuclear genome and imported into plastids. Once there, protein quality control systems ensure proper folding of the mature forms and remove irreversibly damaged proteins. The Ser-type Clp protease is the main machinery for protein degradation of in the plastid stroma. Our work with deoxyxylulose 5-phosphate synthase (DXS), the main flux-controlling enzyme in the plastidial isoprenoid pathway, has shown that the Clp protease complex acts in coordination with nuclear-encoded plastid-targeted chaperones for the control of both enzyme levels and proper folding (i.e. activity). This cross-talk involves a retrograde signaling pathway similar to unfolded protein response mechanisms characterized in mitochondria and endoplasmic reticulum. Coordinated Clp protease and chaperone activities appear to further influence other plastid processes, including the differentiation of chloroplasts into carotenoid-accumulating chromoplasts during tomato fruit ripening.