Pompe disease is a rare autosomal recessive, progressive, and often fatal neuromuscular disorder caused by deficiency of lysosomal acid α-glucosidase. It is characterized by the accumulation of glycogen in muscle tissue that leads to progressive muscle weakness and loss of function. In general, there is a good corelation between the severity of residual enzyme activity and the severity of clinical phenotype. Classical infantile form (early-onset) has no enzyme activity and is associated with severe muscle weakness, cardiomyopathy, respiratory failure and death occurs usually within the first year. Late-onset Pompe disease has some residual α-glucosidase activity. The clinical hallmark of adult-onset α-glucosidase deficiency is slowly progressive myopathy. However, some adult forms present with certain phenotypic diversity. The course of adult-onset form was usually progressive, disabling and often fatal. Determination of deficient α-glucosidase activity in a dried blood spot provides a rapid and reliable diagnostic method for Pompe disease, especially as the initial screening test. The diagnosis of Pompe disease is definitively confirmed by measurement of decreased enzyme activity in leukocytes, cultures of fibroblasts or muscle tissue. Pompe disease can be diagnosed also by DNA testing, verification of respective mutation in the gene for acid alfa-glucosidase. There was no treatment for Pompe disease until recently. The recent development of recombinant α-glucosidase has dramatically improved the life expectancy and quality of life with improvements of muscle motor and muscle respiratory functions in all forms of Pompe disease. This article focuses on the pathogenesis, clinical presentation, diagnosis and enzyme replacement therapy for Pompe disease.