Diflucan (fluconazole) typically starts working within 24 to 72 hours after administration. For common infections like vaginal yeast infections, symptoms such as itching and discharge often begin to improve within the first 24 to 48 hours. However, full resolution of the infection may take longer, sometimes up to one to two weeks depending on the severity and type of infection. More severe or systemic fungal infections may require longer treatment before symptom relief is noticeable. It is important to complete the full course of treatment as prescribed to ensure the infection is fully eliminated and to prevent recurrence.