Pseudomonas aeruginosa is one of the common species responsible for an array of diseases in the respiratory tract, gastrointestinal tract, urinary tract, bones, joints and different systemic infections of normal and immunocompromised patients as well. It exhibits resistance to a wide variety of antimicrobial agents and expresses diverse molecular epidemiology to various established classes of antibiotics including β-lactams, fluoroquinolones, tetracycline and aminoglycosides. Despite the low permeability, hydrophilicity and nonspecific behavior of the outer membrane to small molecular transport, it is inadequate to explain the degree of resistance in P. aeruginosa. The resistance mechanism of P. aeruginosa against various chemical agents is due to the complex chromosomally encoded genes. Different strains of P. aeruginosa having the inherent capacity for biofilm formation, further boosts the resistance under various environmental factors. This chapter explains pathogenicity, mode and types of resistance of P. aeruginosa, its impact on the economy and available remediation/reduction measures and treatments.