Almost any process in life is accompanied by heat changes which can be monitored by isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC). Both techniques are now established tools in fundamental research but over the last decade a clear tendency towards more problem-driven applications is noted. This review aims at summarizing these problem-oriented applications of microcalorimetry and the solutions both techniques can provide to problems in biotechnology. The biotechnological issues to which microcalorimetry has been successfully applied are as diverse as rational drug design, overcoming drug resistance, optimization of long-term stability of proteins, estimation of the bioavailability of drugs, control of complex pharmaceutical products or the optimization of gene delivery efficiency. The main limitation of microcalorimetry, which is the relatively large amounts of sample necessary for analysis, is less important in the biotechnology sector which frequently uses large-scale produced bulk products for analysis. The recently developed high-throughput DSC and ITC microcalorimeters will additionally reduce the labour intensity of these techniques. Due to the precision of microcalorimetric analyses and the versatility of processes which can be studied, it is expected that ITC and DSC will soon be key technologies in biotechnological research.