Group B streptococcus (GBS; Streptococcus agalactiae) is a globally disseminated opportunistic pathogen that causes sepsis, meningitis, pneumonia and soft-tissue infections in healthy or immunocompromised adults. GBS is the leading cause of neonatal infections with 0.6 cases/1000 live births and 6% mortality rate in Australia. GBS is usually a commensal of the genitourinary tract but colonizes a variety of niches within the body and is capable of residing inside host cells in the intracellular environment. Antimicrobial metal ions such as zinc or copper are concentrated within host cells as an immune response to kill invading pathogens. Bacteria possess import and efflux mechanisms to fine-tune Zn or Cu levels, such that free ions remain diminishingly low inside the bacterial cytoplasm. We recently elucidatedmechanisms of Zn and Cu resistance in GBS and defined the regulation of efflux by metal ion responsive transcription factors. By combining metal-ion survival assays, mutational and transcriptional analyses, and in vitro and in vivo disease models, we show that resistance to Zn and Cu significantly alters the ability of GBS to survive within the host and cause disseminated infection. In addition, our data show that hypervirulent GBS isolates are more susceptible to killing by Zn or Cu. Together, our observations highlight novel aspects of Zn and Cu resistance strategies in GBS that could be targeted in future therapeutic approaches for GBS treatment and prevention.