Introduction: In the ophthalmologic field is not uncommon to find signs and symptoms derived from systemic pathologies. Such cases demand a comprehensive approach that allows full control of the ophthalmic manifestations that can be as severe as ulceration or ocular perforation. Case presentation: We describe three cases of Sjogren’s syndrome based on ocular and oral symptoms as well as salivary gland biopsy and presence of auto-antibodies, who received conventional topical treatment and systemic immunosuppression and were expected to improve his symptoms and prevent progression of the disease. However, after identifying the failure of this treatment, we decided to switch to biologic therapy with rituximab. Conclusions: After therapy with steroids or immunosuppressants has failed, treatment with rituximab should be considered. Improvement in objective variables like Schirmer’s test and ocular surface stain as well as subjective component of symptoms and comfort can be achieved.