Nowadays defying homology relationships among sequences is essential for biological research. Within homology the analysis of orthologs sequences is of great importance for computational biology, annotation of genomes and for phylogenetic inference. Since 2007, with the increase in the number of new sequences being deposited in large biological databases, researchers have begun to analyse computerized methodologies and tools aimed at selecting the most promising ones in the prediction of orthologous groups. Literature in this field of research describes the problems that the majority of available tools show, such as those encountered in accuracy, time required for analysis (especially in light of the increasing volume of data being submitted, which require faster techniques) and the automatization of the process without requiring manual intervention. Conducting our search through BMC, Google Scholar, NCBI PubMed, and Expasy, we examined more than 600 articles pursuing the most recent techniques and tools developed to solve most the problems still existing in orthology detection. We listed the main computational tools created and developed between 2011 and 2017, taking into consideration the differences in the type of orthology analysis, outlining the main features of each tool and pointing to the problems that each one tries to address. We also observed that several tools still use as their main algorithm the BLAST “all-against-all” methodology, which entails some limitations, such as limited number of queries, computational cost, and high processing time to complete the analysis. However, new promising tools are being developed, like OrthoVenn (which uses the Venn diagram to show the relationship of ortholog groups generated by its algorithm); or proteinOrtho (which improves the accuracy of ortholog groups); or ReMark (tackling the integration of the pipeline to turn the entry process automatic); or OrthAgogue (using algorithms developed to minimize processing time); and proteinOrtho (developed for dealing with large amounts of biological data). We made a comparison among the main features of four tool and tested them using four for prokaryotic genomas. We hope that our review can be useful for researchers and will help them in selecting the most appropriate tool for their work in the field of orthology.