Skeletal muscle weakness is common in the intensive care units (ICU). Approximately 50% of patients under mechanical ventilation for more than 7 days show signs of ICU-acquired muscle weakness. In these patients, muscle weakness may be the result of axonal polyneuropathy, myopathy or a combination of both. The commonest risk factors in patients with ICU-acquired weakness (AW) are the severity and duration of the systemic inflammatory response, duration of the stay in the ICU and of mechanical ventilation, hyperglycemia, hypoalbuminemia, parenteral nutrition, and administration of corticosteroids and of neuromuscular blocking agents. Loss of thick filaments (myosin), atrophy of the myofibers, necrosis, and regeneration features has been consistently shown in muscle samples during critical illness. Moreover, a slow-to-fast fiber type shift, reduced muscle fiber cross-sectional area of the myofibers, alterations in muscle contractility, reduced aerobic capacity and protein synthesis, and the electromechanical properties of the nerve-muscle interface are also relevant features in skeletal muscles of critically ill patients and experimental models. Several diagnostic tools are currently available to identify patients at risk of ICU-AW. Early rehabilitation in combination with nutritional support constitutes the basis of the therapeutic strategies to be implemented in ICU. Future research will need to shed light on additional cellular processes that could also be targeted pharmacologically. An overview of all these aspects has been provided during the Second International Symposium on Acute Pulmonary Injury Translational Research organized by Hospital Universitario de Getafe (Madrid, Spain) in November 2017 and it is being described in the present review.