**1. Introduction**

Infections caused by a variety of bacterial, fungal, viral, and other infectious microorganisms are considered to be the world's most leading problem. Infectious diseases are considered to be the world most leading cause of death, with almost 50,000 deaths per day [1]. Bacterial and fungal infections are the major cause of morbidity and mortality in both developed and developing countries [2]. *Staphylococcus aureus* is a gram-positive, coagulase-positive opportunistic bacterial pathogen, commonly found in the human nasal mucosa in the approximately 20–40% population [3, 4]. It causes a wide range of infections such as skin infections, including abscesses, impetigo, and necrotizing fasciitis; tissue infections, including osteomyelitis and endocarditis; and toxicities, including toxic shock syndrome, pneumonia, sepsis, and surgical site infections [5–7]. The superficial and invasive infections caused by *S. aureus* continue to raise serious health challenges globally as it notoriously exhibits resistance [8, 9]. These infections have rapidly developed resistance against most of the available antimicrobials, which pose serious threats [10–13]. Infections caused by *S. aureus* are associated with significantly higher mortality, because of the limitations of available antimicrobial therapies, difficulties in making a rapid and accurate diagnosis, and the development of multidrug resistance (MDR) [14]. The acute and chronic staphylococcal infections have now become more problematic after emerging multidrug resistance (MDR) against various frontline antibiotics [15, 16]. Antibiotics are small molecules that selectively inhibit the growth of a plethora of bacterial and other infections. These heterogeneous group molecules continue to be save many lives from different bacterial infections. Antibiotics are either naturally synthesized by microorganisms or chemically modified into exciting drugs. β-lactam antibiotics (β-LA) are considered to be the most successful and frequently used antibiotics against a number of bacterial infections. The underlying reason behind this is their wide spectrum activity, oral availability, excellent pharmacokinetics, lack of toxicity, and bactericidal action [17]. Due to the widespread and prolonged practice of β-LA emerged resistance to these resort and became an alarming and emerging problem to the public health. The microbial pathogens tend to adopt different resistance mechanism to skip the cytotoxic effect of β-LA. The progression in β-LA drug resistance to emerge multiple antibiotic-resistant microorganisms has made it difficult to manage many infectious diseases using common anti-infective drugs. In this chapter, we focus on emerging trends of drug resistance in *S. aureus* to the different β-LA.
