Stress in plants could be defined as any change in growth condition(s) that disrupts metabolic homeostasis and requires an adjustment of metabolic pathways in a process that is usually referred to as acclimation. Metabolomics could contribute significantly to the study of stress biology in plants and other organisms by identifying different compounds, such as by-products of stress metabolism, stress signal transduction molecules or molecules that are part of the acclimation response of plants. These could be further tested by direct measurements, correlated with changes in transcriptome and proteome expression and confirmed by mutant analysis. In this review, we will discuss recent application of metabolomics and system biology to the area of plant stress response. We will describe approaches such as metabolic profiling and metabolic fingerprinting as well as combination of different 'omics' platforms to achieve a holistic view of the plant response stress and conduct detailed pathway analysis.