Each year in the United States, 2 million people are infected with antibiotic-resistant pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA), with 23,000 patients dying from such infections. The increase in antibiotic resistance and slow development of antibiotics have created an urgent need for new approaches to treat infections, including “Immune boosting” approaches that target the host. One target of such approaches may be G protein-coupled receptors (GPCRs) expressed by neutrophils, critical first-line effectors of innate immune defense against pathogens. To date, a relatively limited number of GPCRs have been studied in the context of neutrophil function. Using qPCR-based gene expression arrays and RNAseq, we have found that neutrophils express ~190 (of the ~360 known) non-chemosensory (i.e., other than visual, odorant or taste) GPCRs. Many of these GPCRs have unknown or poorly understood roles in neutrophil function. We propose targeting such GPCRs to enhance the antimicrobial response of neutrophils via modulation of chemotaxis/phagocytosis and the production of neutrophil extracellular traps (NETs). Such approaches may provide a novel way selectively boost the innate immune response to pathogens.