The second generation of antipsychotics (SGA) are an pharmacological heterogeneous group which is characterized by superiour efficacy on the negative, positive, affective and cognitive symptoms of schizophrenia. If this group is psychopharmacological different it is to anticipate a different clinical efficacy on the four clinical dimensions of schizophrenia. This allow an individual use of them. The clinical experience shows that it is a correlation between the SGA mechanism of action, clinical efficacy and side effect profile. Amisulpride has an ultraselected antidopaminergic mechanism is correlated function of dose with a higher efficacy on positive and negative symptoms. Multi-acting receptor targeting antipsychotics (e.g. Olanzapine, Quetiapine) have a similar clinical efficacy on the positive, negative and affective symptoms but they have an individual risk of side effects appearance (e.g. weight gain, diabetes, QTc interval prolongation. Ziprasidone is a particular SGA with antagonist effect on r.5-HT2A, r.5-HT2C, r.5-HT1D and the agonist effect on r.5-HT1A. This is correlated with a high efficacy on the negative and depressive symptoms. Aripiprazole is a modulator and stabilizer of dopamine activity with a dual mechanism of action (antagonist/agonist. It has a long term efficacy on positive and negative symptoms but this effect isn't correlated with dose.