Plants growing in natural environments are exposed to a broad range of biotic (pathogen attack, insect herbivory, etc.) and abiotic factors (drought, extreme temperatures, UV radiation, salinity, etc.) that are known to cause stress symptoms in many species (Pareek et al., 2010; Robert-Seilaniantz et al., 2010). Biotic and abiotic stress-inducing determinants often adversely impact plant growth and development, frequently leading to severe annual yield losses in agricultural production (Pierik et al., 2013; Pieterse et al., 2012; Stam et al., 2014). In the research endeavors described in this thesis, Arabidopsis thaliana was used as a model organism to study plant responses to different sequential combinations of biotic factors (infection with Botrytis or herbivory by Pieris) and drought. The main objective was to identify genes that contribute to tolerance to the aforementioned sequential stress combinations. Genome-wide association (GWA) mapping and RNA sequencing (RNA-seq) approaches were used to identify combinatorial stress responsive genes. A number of candidate genes to combinatorial stress responses were identified by GWA analysis and RNA-seq. The physiological function of some candidate genes in different stress conditions were characterized using T-DNA insertion mutants and gene expression study. However, the physiological function of many allelic variants in stress conditions remain to be discovered. The study highlights the importance of an array of genes, crucial to the underlying defense processes, as targets for breeding by allele mining, ultimately aimed at improvement of crop tolerance to frequent combinations of stress factors.