The aim of this study was to assess the influence of drug therapy (DT) with pramiracetam and memory training (MT), each alone, and in combination (DTMT), on both the objective memory and metamemory performance. Thirty-five non-depressed, non-demented healthy elderly (mean age: 64.8 years) with objective (story recall) and/or subjective (cognitive difficulties scale) memory loss were randomly included in four open-label conditions: an MT condition (n = 10), a DT condition (n = 8), a DTMT condition (n = 10), and a control (CTR) condition (n = 7). MT and DTMT subjects participated in 12 real-life tutor-guided MT sessions, once weekly, each lasting 1.5 hrs. The subjects were tested for objective (Randt memory test) and subjective (Sehulster metamemory scale; memory functioning questionnaire) memory proficiency prior to (t(0)) and shortly after treatment (t(1)). Results showed that objective memory gains of the two groups receiving pramiracetam were significantly larger than that of the MT and CTR groups. The ranking order in terms of decreasing score improvements was DTMT - DT - MT - CTR. Metamemory, on the other hand, displayed only a trend to between-group differences with opposite patterns for the DT and DTMT groups. In the DT group, the level of depression, negatively interfered with metamemory but not with actual memory performance. The present findings stress, once again, the complex relationships between memory, metamemory and affective status, which may be differently modified by DT and MT.