Co-cultivation is an effective method of inducing the production of specialized metabolites (SMs) in microbial strains. By mimicking the ecological interactions that take place in natural environment, this approach enables to trigger the biosynthesis of molecules which are not formed under monoculture conditions. Importantly, microbial co-cultivation may lead to the discovery of novel chemical entities of pharmaceutical interest. The experimental efforts aimed at the induction of SMs are greatly facilitated by computational techniques. The aim of this overview is to highlight the relevance of computational methods for the investigation of SM induction via microbial co-cultivation. The concepts related to the induction of SMs in microbial co-cultures are briefly introduced by addressing four areas associated with the SM induction workflows, namely the detection of SMs formed exclusively under co-culture conditions, the annotation of induced SMs, the identification of SM producer strains, and the optimization of fermentation conditions. The computational infrastructure associated with these areas, including the tools of multivariate data analysis, molecular networking, genome mining and mathematical optimization, is discussed in relation to the experimental results described in recent literature. The perspective on the future developments in the field, mainly in relation to the microbiome-related research, is also provided.