Dasatinib is considered an effective treatment agent in imatinib-resistant and newly diagnosed chronic phase CML patients. Patients receiving dasatinib 100 mg once daily regime suffered significantly fewer thrombocytopenia and pleural effusion events than those receving 70 mg twice daily. Effective molecular monitoring and the proper management of pleural effusion during the first-line dasatinib administration in CML are essential. Pleural effusion may develop any time of the treatment and is easily managed by treatment interruption, dose reduction and supportive therapy. In this article, we intended to assess the rational of managing CML and pleural effusion that successfully managed with dose reduction and supportive care.