Bacterial lipoproteins (Lpp) compose a large family of surface-exposed proteins that are involved in diverse, but critical, cellular functions spanning from fitness to virulence. All of them present a common signature, a sequence motif, known as LipoBox, containing an invariant Cys residue that allows the protein to be covalently bound to the membrane through a thioether linkage. Despite the abundance and relevance of Lpp, there is a scarcity of structural and functional information for this family of proteins. In this review, the updated structural and functional data for Lpp from two Gram-positive pathogenic model organisms, Staphylococcus aureus and Streptococcus pneumoniae is presented. The available structural information offers a glimpse over the Lpp functional mechanisms. Their relevance in bacterial fitness, and also in virulence and host-pathogen interactions, reveals lipoproteins as very attractive targets for designing of novel antimicrobials, and interesting candidates as novel vaccine antigens.