Photorespiration, one of the cornerstone pathways of primary metabolism, allows plant growth in a high oxygen-containing environment. While the oxygenase reaction of Rubisco directly influences photosynthesis per se, several other processes are also affected by photorespiration, including nitrogen assimilation, respiration, amino acid metabolism, 1-C metabolism and redox metabolism, cumulating to impose a severe impact across multiple signalling pathways. Accordingly, although the plant photorespiratory cycle is complex and highly compartmentalised, little is currently known about the participating transport proteins, and relatively few of them have been properly identified. Despite its centrality, uniqueness, and mystery, the biochemistry of photorespiration has historically been quite poorly understood, in part because at least some of its enzymes and intermediates tend to be labile and of low abundance. Fortunately, the integration of molecular and genetic approaches with biochemical ones, such as metabolite profiling, is now driving rapid advances in knowledge of the key metabolic roles and connections of the enzymes and genes of the photorespiratory pathway. While these experiments have revealed a surprising complexity in the response and established connections between photorespiration and other metabolic pathways, the mechanisms behind the observed responses have still to be fully elucidated. Here we review recent progress into photorespiration and its interaction with other metabolic processes, paying particular attention to data emanating from metabolic profiling studies.