Bovine anaplasmosis is an infectious non-contagious disease transmitted mainly by ticks or fomites contaminated with Anaplasma marginale. Once cattle have developed the disease it can be treated with antibiotics or chemotherapy, although with partial success. Still, there is no effective and global prophylactic method available, mainly because of variability and diversity showed by different A. marginale strains distributed worldwide. In this regard, several proteins have been proposed as immunogens, MSPs, OMPs, Type IV Secretion System Proteins and some other hypothetical proteins, which have been chosen either by experimental evidence or more recently by genome-based analysis. So far, the results suggest that a single molecule will not be enough to trigger a protective immune response in the host, so it is necessary to identify other proteins or epitopes with adequate immunological properties, a process in which omics tools have potential. In order to develop a vaccine against bovine anaplasmosis, it has been proposed by the use of combinations of molecules, exposure formats and application protocols to provide an effective control of the disease.