This chapter discusses about the infections in immunocompromised patients in ICU. Life-threatening infections occur frequently in immunocompromised patients with chronic diseases. Complicated diabetes mellitus (DM), chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), or chronic liver disease are life-threatening infections. Life-threatening infections that occur in patients with chronic medical diseases, namely DM, COPD, CKD, cirrhosis, and heart failure (HF), are presented here. Diabetes mellitus is associated with increased risk of urinary tract infections (UTIs), skin and soft tissue infections (SSTIs), and lower respiratory tract infections. Acute exacerbation, community-acquired pneumonia, invasive pulmonary aspergillosis are specific infections of COPD. CKD is a global public health problem. Catheter-related bloodstream infections, peritonitis and community-acquired pneumonia are specific infections of CKD. In the United States, approximately 15% of the population has chronic liver disease, with cirrhosis being a major cause of death worldwide. Spontaneous bacterial peritonitis, community-acquired pneumonia, skin and soft tissue infections, community-acquired bacterial meningitis and endotipsitis are specific infections of chronic liver disease. HF is a risk factor for admission of patients with CAP into the ICU.