Due to their sessile lifestyle, plants are exposed to a large set of environmental cues. In order to cope with changes in environmental conditions a multitude of complex strategies to regulate metabolism has evolved. The complexity is mainly attributed to interlaced regulatory circuits between genes, proteins and metabolites and a high degree of cellular compartmentalization. The genetic model plant Arabidopsis thaliana was intensely studied to characterize adaptive traits to a changing environment. The availability of genetically distinct natural populations has made it an attractive system to study plant-environment interactions. The impact on metabolism caused by changing environmental conditions can be estimated by mathematical approaches and deepens the understanding of complex biological systems. In combination with experimental high-throughput technologies this provides a promising platform to develop in silico models which are not only able to reproduce but also to predict metabolic phenotypes and to allow for the interpretation of plant physiological mechanisms leading to successful adaptation to a changing environment. Here, we provide an overview of mathematical approaches to analyze plant metabolism, with experimental procedures being used to validate their output, and we discuss them in the context of establishing a comprehensive understanding of plant-environment interactions.