Water-soluble CdSe quantum dots (QDs) capped with l-cysteine (Cys-CdSe) were synthesized in aqueous medium and analyzed by X-ray diffraction, electronic microscopy, absorption spectroscopy and time-resolved fluorescence spectroscopy. We have measured the average diameter of Cys-CdSe QDs, 4.15 nm, the true molecular mass, 1.43 × 105 g mol−1 and the molar extinction coefficient, ε480 = 3 × 105 cm−1 M−1 at maximum of band edge (480 nm). The number of grafted l-cysteine chains per individual QD was measured to be ∼100. The interaction of these functionalized Cys-CdSe QDs at a concentration of 0.2 μM with seventeen different metal ions were evaluated by fluorescence. Only the interaction with Co2+ ions resulted in fluorescence quenching in the range 0.5–20 μM when the true concentration of QDs is 0.2 μM, with a saturation behavior at Co2+ concentration of ∼20 μM, in agreement with 100 grafted l-cysteines per QD. The quenching mechanism involves both static and dynamic fluorescence quenching processes. A model of interaction is derived for the selective binding of Co2+ to Cys-CdSe QDs, involving the carboxyl functions of l-cysteine. The comparison with other QD-systems shows the need for a systematic analysis of the parameters influencing the QD-ions interaction and fluorescence emission, especially their true concentration, in order to understand the fundamental mechanisms at the origin of the specificity for metal binding to a particular QD.