Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) imaging mass spectrometry, also called MALDI-imaging, is a label-free bioanalytical technique used for spatially-resolved chemical analysis of a sample. Usually, MALDI-imaging is exploited for analysis of a specially prepared tissue section thaw mounted onto glass slide. A tremendous development of the MALDI-imaging technique has been observed during the last decade. Currently, it is one of the most promising innovative measurement techniques in biochemistry and a powerful and versatile tool for spatially-resolved chemical analysis of diverse sample types ranging from biological and plant tissues to bio and polymer thin films. In this paper, we outline computational methods for analyzing MALDI-imaging data with the emphasis on multivariate statistical methods, discuss their pros and cons, and give recommendations on their application. The methods of unsupervised data mining as well as supervised classification methods for biomarker discovery are elucidated. We also present a high-throughput computational pipeline for interpretation of MALDI-imaging data using spatial segmentation. Finally, we discuss current challenges associated with the statistical analysis of MALDI-imaging data.